This is a multi-method, longitudinal study of the developmental pathways to violence/victimization and substance use (VVSU) as risks for gun violence, in a sample characterized by high pre and postnatal risks. Mother-infant dyads (n = 216) were originally recruited at birth for a study of developmental outcomes associated with prenatal cocaine exposure. The sample is well suited to examining developmental pathways to VVSU due to the accumulation of pre and postnatal risks and the focus on developmental mechanisms of interest using observational, physiological, maternal, child, and teacher report measures at critical time points beginning in infancy. The current application examines developmental pathways leading to weapon carrying, gang involvement, and co-occurring VVSU in later adolescence. A major focus of this application is on developmental mechanisms explaining this risk. One primary mechanism is through a reactive aggression pathway with pre and perinatal risks and exposure to violence predicting VVSU in later adolescence (15-17 years) via high physiological and behavioral reactivity and low regulation in response to frustration from infancy to school age; reactive aggression, cognitive processes such as hostile attribution bias and substance use norms, peer bullying and victimization, and low parental monitoring in early adolescence (12-14), and continuing harsh parenting from infancy to adolescence. A second mechanism is a proactive aggression pathway with early exposure to violence and temperamental fearlessness in infancy predicting VVSU in later adolescence via low conscience and non-normative aggressive trajectories in childhood; proactive aggression, positive outcome expectancies for aggression and substance abuse, peer deviance, low parental monitoring, and parental support for aggression in early adolescence, and exposure to harsh parenting from infancy to adolescence. The role of community risk factors (e.g., activity space, high crime neighborhoods) will be examined as potential predictors, mediators, or moderators of risk. Finally, exploratory analyses will focus on protective factors predicting resilience, reciprocal associations over time, and gender differences. Few studies have examined the etiology of co-occurring violence, victimization, and substance use using theoretically driven etiological models that include critical risk and protective factors from infancy to adolescence using a diverse, high risk sample and multiple methods focused on developmental mechanisms that may mediate or moderate outcomes. Understanding these mediating and moderating mechanisms of violence and substance use are critical to informing content and timing of preventive interventions. This high risk sample is also well suited to advance one major initiative of the National Institutes of Health: understanding the etiology of gun violence including underlying mechanisms of violence, cognitive, behavioral, and physiological determinants of violence, and risk and protective factors operating at multiple levels of analysis (individual, family, community).